Medical Drug Criteria (MDC)

Policy Num:       P1.002.014
Policy Name:     AMTAGVI (Lifileucel)
Policy ID:          [P.1.002.014] [Ac /  L / M+ / P+ ] 

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related MDC: NONE

AMTAGVI (Lifileucel)

Summary

Amtagvi (lifileucel) is an autologous TIL (tumor-infiltrating lymphocyte) therapy approved by the FDA in February 2024 for the treatment of unresectable or metastatic melanoma in adults who have failed anti–PD-1 immunotherapy and, if BRAF V600 positive, targeted therapy with BRAF ± MEK inhibitors. The approval is accelerated, and continued approval is contingent upon confirmatory evidence of clinical benefit.

Policy Statements

Approved only for unresectable or metastatic melanoma after documented failure of anti–PD-1 therapy and, if applicable, BRAF-targeted therapy.

One-time infusion therapy, highly specialized, available only in authorized treatment centers.

Policy Guidelines

Triple S Salud considers lifileucel (Amtagvi) medically necessary for the treatment of unresectable or metastatic melanoma in members 18 years and older when all of the following criteria are met:

1. The member has received prior treatment with the following drug categories:

   1. PD-1 blocking antibody (e.g., Keytruda, Opdivo); and
   2. BRAF inhibitor (e.g., Braftovi, Tafinlar, Zelboraf) with or without a MEK inhibitor (e.g., Cotellic, Mekinist, Mektovi) if BRAF V600 mutation positive; and
2. The member has not received previous treatment with the requested medication; and
3. The member does not have uveal or ocular melanoma; and
4. The member does not have uncontrolled brain metastases; and
5. The member has not had organ allograft (except kidney transplant) or prior cell transfer; and
6. The member has adequate and stable kidney, pulmonary and cardiac function; and
7. The member has an ECOG performance status of 0 or 1; and
8. The member does not have clinically significant active infection.

Triple S Salud considers all other indications as experimental, investigational.

DOSAGE/ADMINISTRATION

Lifileucel is supplied as Amtagvi, a cell suspension, for intravenous infusion. A single dose of Amtagvi contains 7.5 x 10⁹ to 72 x 10⁹ viable cells suspended in 1 to 4 person-specific infusion bag(s). Amtagvi is for autologous and intravenous use only. Verify the person's identity prior to infusion. Amtagvi is provided as a single dose for infusion.

• Administer Amtagvi in an in person hospital setting with an intensive care facility.
• The Amtagvi dose is between 7.5 x 10⁹ and 72 x 10⁹ viable cells.
• Administer a lymphodepleting regimen before infusion of Amtagvi.
• Do not use a leukocyte depleting filer with Amtagvi.
• Premedicate the person with acetaminophen, or equivalent, and diphenhydramine, or another H1-antihistamine.
• Avoid prophylactic use of systemic corticosteroids.
• Administer entire dose of Amtagvi.
• Administer IL-2 (aldesleukin) after infusion of Amtagvi.
• See full prescribing information for instructions on receipt, preparation, and administration of Amtagvi.

Source: Iovance Biotherapeutics Manufacturing, 2024

REQUIRED MEDICAL INFORMATION

Age ≥18 years.

Histologically confirmed unresectable or metastatic melanoma (stage IIIC or IV).

Documented progression following:

• Anti–PD-1 therapy (e.g., pembrolizumab, nivolumab).
• For BRAF V600–positive patients: failure of BRAF ± MEK inhibitors.
• ECOG performance status 0–1.
• Absence of: uncontrolled infection, significant renal impairment, recent ≥grade 2 bleeding, uncontrolled brain metastases, severe cardiopulmonary compromise, LVEF <45% or NYHA >1, FEV1 ≤60%.

EXCLUSION CRITERIA

Age <18.

Uveal/ocular melanoma.

Uncontrolled brain metastases.

Active systemic infection.

≥Grade 2 bleeding event within the past 14 days.

 LVEF <45% or NYHA class >1; FEV1 ≤60%.

BENEFIT APPLICATION

Prior authorization requiring complete documentation (clinical history, pathology, mutation testing, etc.).

OTHER CRITERIA

N/A

Practice Guidelines and Position Statements

NCCN lists lifileucel (Amtagvi) as a Category 2A, preferred option for patients with advanced disease who have failed prior therapy.

 Clinical trials show an ORR (objective response rate) of ~31.4–31.5%, with durable responses; median duration of response not reached at ~21-month follow-up.

Medicare National Coverage

No national Medicare coverage determination yet; most plans apply case-by-case prior authorization, eligibility, and site-of-care restrictions.

References

1. FDA Approval & Prescribing Information (Feb 2024)
2. Amtagvi Billing & Coding Guide
3. NCCN Position & Outcomes (ORR, mDOR data)
4. Medscape Reference – Safety & Administration

Codes

Applicable Modifiers

Policy History